Blood-stage immunity to Plasmodium chabaudi malaria following chemoprophylaxis and sporozoite immunization

  1. Wiebke Nahrendorf  Is a corresponding author
  2. Philip J Spence
  3. Irene Tumwine
  4. Prisca Lévy
  5. William Jarra
  6. Robert W Sauerwein
  7. Jean Langhorne  Is a corresponding author
  1. MRC National Institute for Medical Research, United Kingdom
  2. Radboud University Medical Centre, Netherlands
6 figures and 1 table

Figures

Overview of experimental procedures.

To quantify transient blood-stage exposure during chemoprophylaxis and sporozoite (CPS) immunization female C57BL/6 were immunized three times at 2-week intervals with P. chabaudi AS-infected …

https://doi.org/10.7554/eLife.05165.003
Chloroquine permits transient blood-stage parasitemia during each immunization.

The number of parasitized erythrocytes (pE) per ml of whole blood was enumerated by quantitative RealTime PCR after each CPS immunization (i1, i2, i3) with P. chabaudi AS-infected mosquito bites …

https://doi.org/10.7554/eLife.05165.004
Pre-erythrocytic immunity following CPS immunization requires high doses of sporozoites.

Liver parasite burden was determined 42 hr after mosquito bite challenge as copy number of P. chabaudi-specific 18S rRNA. (A) Mice were CPS immunized three times (i1, i2, i3) with P. chabaudi

https://doi.org/10.7554/eLife.05165.005
Figure 4 with 1 supplement
CPS immunization elicits blood-stage immunity.

Mice were CPS immunized three times (i1, i2, i3) using chloroquine (CQ) and P. chabaudi AS-infected or uninfected mosquito bites (mock immunized). Approximately 100 days after the final CPS …

https://doi.org/10.7554/eLife.05165.006
Figure 4—figure supplement 1
Chronic blood-stage infection in CPS immunized mice.

Naive infection controls or mice that were CPS immunized three times (i1, i2, i3) using chloroquine (CQ) and P. chabaudi AS-infected mosquito bites were challenged (C) by intraperitoneal (ip) …

https://doi.org/10.7554/eLife.05165.007
CPS immunization elicits heterologous blood-stage immunity.

Mice were CPS immunized three times (i1, i2, i3) under chloroquine (CQ) cover by P. chabaudi AS-infected mosquito bites or mock immunized with uninfected mosquito bites, and challenged (C) 96–107 …

https://doi.org/10.7554/eLife.05165.008
Extended blood-stage parasitemia elicits pre-erythrocytic immunity.

Mice received a first infection with P. chabaudi AS either by mosquito bite (Bite) or intraperitoneal (ip) injection of 10,000 parasitized erythrocytes obtained from a donor mouse infected by …

https://doi.org/10.7554/eLife.05165.009

Tables

Table 1

Relationship between the dose of immunizing pre-erythrocytic and blood-stage parasites and the acquisition of immunity.

https://doi.org/10.7554/eLife.05165.010
Low doseHigh dose
Sporozoites (liver-stage parasites)Mosquito bite or 100 sporozoites iv: no pre-erythrocytic immunity (Figure 3A/B)10,000 sporozoites iv: pre-erythrocytic immunity (Figure 3B)
Blood-stage parasitesBlood-stage infection curtailed by chloroquine: partial blood-stage immunity (Figure 4)Fulminant, self-cured blood-stage infection: blood-stage immunity (Spence et al., 2013); pre-erythrocytic immunity (Figure 6)

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